It has been postulated that axon sprouting may be a mechanism which underlies some recovery of function following brain damage. Ethanol exposure may have deleterious effects on sprouting and recovery regardless of whether the damage is ethanol-induced or induced by trauma. However, almost no information is available concerning whether CNS neurons exposed chronically to ethanol are even capable of sprouting. The purpose of this proposal is to evaluate the effects of ethanol on sprouting in the adult mammalian brain. For several reasons, monitoring the reorganization of the rat dentate gyrus after partial deafferentation (by the unilateral removal of the entorhinal cortex) will be the method used to assess the effects of ethanol on sprouting: 1) unlike ethanol-induced damage, the entorhinal lesion leaves the contralateral region virtually intact, allowing an intraanimal control which increases the power of quantitative analysis; 2) it will provide data directly related to whether trauma-induced sprouting is retarded or inhibited by ethanol; and 3) it permits focusing on the behavioral recovery of a specific deficit that has been linked previously to sprouting. Quantitative methods including computerized image processing of acetyl-cholinesterase (AChE) histochemical and anterograde autoradiographic pathway tracing techniques will be used to evaluate the stereotypic sprouting responses of the septal, commissural, and crossed temperodentate projections to the dentate gyrus. Recovery of function will be evaluated by monitoring changes in spontaneous alternation correlated with neuroanatomical measures of sprouting within the same animals. By determining if long-term ethanol exposure inhibits sprouting and recovery. it will then be possible to assess whether abstinence has a positive (recoupable) affect on sprouting and recovery. These data will be important for developing and modifying theories to account for the reversibility and recovery from ethanol-induced and lesion-induced brain damage in alcoholics.